1. Field of the Invention
The current invention concerns a method for treatment of bacterial infections with rifalazil administered once-weekly or twice-weekly. In particular, the invention concerns a method for treatment of tuberculosis caused by Mycobacterium tuberculosis, infections caused by Mycobacterium avium complex, infections caused by Chlamydia pneumoniae and infections caused by Helicobacter pylori by administering to a patient suffering from the bacterial infection rifalazil once or twice a week. In this dose regimen, the treatment is fast, efficacious and eliminates undesirable secondary symptoms observed with daily doses of 1-50 mg of rifalazil.
2. Background and Related Disclosures
Bacterial infection caused by mycobacterium species and similar infections caused by Chlamydia pneumoniae or H. pylori cause serious health problems in the United States and worldwide. For example, tuberculosis, caused by Mycobacterium tuberculosis is one of the most serious infectious diseases outside of developed countries, with over one billion people infected worldwide. The worldwide infection rate results in eight million active tuberculosis cases annually and over two million deaths per year. In the United States, 26,000 new cases of active tuberculosis were reported in 1994. The number of active cases in the United States is high because of the increase in patients with AIDS and the increase in immigration from developing countries. Moreover, there is reported an increase in multidrug resistance tuberculosis and disseminated Mycobacterium avium complex infections.
Additionally, there is an increase in transmissible chlamydial diseases caused by Chlamydia pneumoniae, nonmotile, obligate intracellulare to bacteria. Chlamydia pneumoniae causes respiratory infections, such as pneumonia, bronchitis, pharyngitis and sinusitis, and has been associated with about 10% of community-acquired pneumonia. The Chlamydia pneumoniae infections are geographically wide spread. Studies on antibody prevalence have shown that large number of people is infected with Chlamydia pneumoniae at one time or another.
Helicobacter pylori infections are infections of gastrointestinal tract. H. pylori is a gram-negative microphilic organism residing in human stomach and intestine which is closely connected with acute gastritis and development of inflammation of mucous layer. Acute gastritis is associated with epigastric pain, nausea and vomiting. The organism is difficult to treat, delayed recurrences are frequent, and treatment involves multiple antibiotic regimens.
It would thus be highly advantageous to provide a method for treatment of the above-described diseases with new types of antibiotics which are able to efficaciously treat and/or eradicate the bacteria or organisms causing these diseases without necessity to utilize complex antibiotic treatments and regimens which result in undesirable secondary symptoms and adverse reactions.
It is, therefore, an object of this invention to provide a method for treatment of Mycobacterium species, Chlamydia pneumoniae and H. pylori infections with once a week or twice a week administration of a relatively new antibiotic, rifalazil, that belongs to the class of antibiotics called ansamycins. Rifalazil has the same or better activity than either rifabutin or rifampin, the other two antibiotics of the same class and actively inhibits the growth of Mycobacterium tuberculosis, Mycobacterium avium species, Chlamydia pneumoniae and H. pylori when administered only once a week or twice a week in doses from 1 to 50 mg. Previously, rifalazil has been administered on daily basis and because of the severe secondary adverse reactions, was discontinued as a drug for treatment of tuberculosis and other infection. Newly discovered once-week or twice-week regimen has the same efficacy as daily administration and yet eliminates or significantly decreases the adverse reactions.
Rifalazil compound has been described in the U.S. Pat. No. 4,983,602 where its antibacterial activity has been disclosed. Dosages described in vitro and in mice animal models correspond to a dose from 10 mg to 10 g/day for adults. However, when clinical trials with these doses of the antibiotic were administered daily, many adverse reactions occurred and the treatment with rifalazil was discontinued.
All patents, patent applications and publications cited herein are hereby incorporated by reference.